The goal of this project is to develop and optimize MR imaging biomarkers for the assessment of breast cancer response to pre-operative treatment. The project is a continuation of effort under Academic-Industrial Partnership (AIP) R01 grant award CA 13270 entitled Real-time in vivo MRI biomarkers for breast cancer pre-operative trials. In the prior funding cycle researchers at UCSF and Hologic (formerly Sentinelle Medical) developed and deployed dedicated workstations to perform volumetric analysis of breast MR images in the multi-center I- SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And molecular analysis) clinical trial. We successfully migrated the signal enhancement ratio (SER) tumor volume measurement method, developed at UCSF and used in the American College of Radiology Imaging Network (ACRIN) trial 6657, to the Hologic Aegis software platform. The Aegis SER software plug-in received IDE approval in 2010 for use in the I-SPY 2 TRIAL and Aegis systems were installed at the 20 I-SPY 2 clinical centers. Tumor volume measurements generated from the Aegis SER plug-in software are now incorporated in the adaptive phase II trial design for I-SPY 2 and used in the patient randomization algorithm. Under a second aim in the original project period, we developed automated image analysis tools to explore how quantification parameters influence the effectiveness of imaging metrics for predicting clinical outcomes. The continuing project focuses on expanding Aegis software functionality to include real-time analysis of diffusion-weighted MRI (DWI) for assessing response, and prospectively testing imaging metrics that have been optimized using the automated tools developed in the previous project period. The work proposed will be coordinated with the I-SPY 2 trial and its imaging sub-study ACRIN 6698, testing breast DWI for assessment of tumor response. Under Specific Aim 1 we will add DWI image analysis and reporting capabilities to the Aegis workstation for measuring breast tumor apparent diffusion coefficient (ADC). Under Specific Aim 2 we will prospectively test the predictive performance of breast cancer subtype-optimized FTV metrics estimated by the retrospective analysis of I-SPY 1 data. The prospective studies will be performed using data from an independent cohort of patients enrolled in the control arm of I-SPY 2. Exploratory studies will also be performed to investigate and compare alternative metrics using DCE and DWI image data from I-SPY 2.